ATP-gated channels in vascular smooth muscle cells.
ATP acting through P2x-purinoceptors activates cation channels with some similarities to the activation of channels gated by acetylcholine and glutamate (channels that can also act as fast excitatory transmitters). These experiments clearly demonstrate an ATP-mediated Ca2+ influx through agonist-gated channels and a consequent elevation of [Ca2+]i in these single vascular smooth muscle cells. The combination of the ability to hold these cells under voltage-clamp and to measure [Ca2+]i simultaneously has allowed us to exclude other possible explanations for the rise in [Ca2+]i under these conditions. Thus, although the major cation entering through the channels is Na+, ATP receptor activation will also generate subtle, localized increases in [Ca2+]. These increases might directly activate contractile proteins or, if insufficient to do this, might upregulate other Ca2(+)-dependent enzymes modulating the contractile process and provide an enhanced source of Ca2+ for uptake into internal Ca2+ stores. Further understanding of the physiological role of this conductance pathway may require the development of specific receptor antagonists or channel blockers.
Benham
C D
CD
Department of Pharmacology, Smith Kline & French Research, Ltd., Welwyn, Herts, England.
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*
D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D002118:Calcium